1. Field of the Invention
The present invention relates to a process for the production of .alpha.-unsaturated amines. More particularly, it relates to an improved process for the production of .alpha.-unsaturated amines useful as insecticides and their intermediates of 1,1,1-trihalogeno-2-nitroethanes.
2. Description of the Prior Art
.alpha.-Unsaturated-amines of the formula (V) shown hereinbelow or their salts are excellent insecticidal compounds [cf. EP-302389A]. As intermediates for production of the same, 1,1,1-trihalogeno-2nitroethanes are known to be prepared by the methods of the following formulas [1] and [2]. ##STR1## [cf. Izvest. Akad. Nauk S.S.S.R., Otdel. Khim. Nauk, 1958, 841 (C.A., 53, 1111i (1959))]. ##STR2##
However, the method of the formula [1] mentioned above which reacts 1,1-dichloroethylene with nitryl chloride shows the disadvantages that nitryl chloride is explosive [cf. Ber. 75 B, 1323(1942)]; its generation must use fuming nitric acid and chlorosulfonic acid which are dangerous and difficult to handle; a large amount of waste sulfuric acid must be disposed of and the yield of the object compound is low. The method of the formula [2] has many problems that very toxic dinitrogen tetroxide and chlorine gas must be used and the yield of the object compound is also low.
Also, the method of the formula [3] is known as the reaction of 1,1-dihalogenoethylene with nitric acid. ##STR3## [cf. Probl. Organ. Sinteza. Akad. Nauk. S.S.S.R., Otd. Obshchi. Tekhn. Khim. 1965. 60 (CA. 64, 8023b (1966))]. However, it is reported that the yield of this reaction is extremely low, i.e., 10.6% of 1,1-dichloro-2-nitroethylene and 37% of nitroacetyl chloride, respectively.
On the other hand, the methods of the formulas [4] and [5] are known to introduce a nitro group and fluorine atom into 1,1-dihalogenoethylene (the latter is supposed to show reactivity entirely different from chlorine and bromine atoms). ##STR4## [Izv. Akad. Nauk SSSR, Set. Kim., 1963, 1946(cf. CA. 60, 5325 g)] ##STR5## [Dokl. Akad. Nauk SSSR, 149, 330-333 (1963) (cf. CA. 59, 6215 g)]
Also, improvements on the above methods [4] and [5] are disclosed in DE 3,305,201 and DE 3,305,202, which however do not afford 1,1,1-trichloro or tribromo-2-nitroethane as the object compound and further do not suggest or teach to react olefins with hydrogen chloride or hydrogen bromide and nitric acid to introduce chlorine or bromine atom as well as nitro group.
The reaction of halogenated olefins with hydrogen chloride or hydrogen bromide requires use of a catalyst such as a metal chloride or active carbon, because their reactivity is less due to a reverse inductive effect (-I effect) of the halogen atom in the halogenated olefins. For instance, anhydrous ferric chloride is used in the reaction of 1,1-dichloroethylene with hydrogen chloride (cf. U.S. Pat. No. 2,209,000).
On the other hand, the reactivity of hydrogen fluoride is different from that of other hydrogen halides. For instance, hydrogen fluoride is required to react with common olefins under pressure, although they tend to react with hydrogen chloride or hydrogen bromide at room temperature [cf., J. Org. Chem., 3, 26(1938)]. Also, hydrogen fluoride is highly reactive with halogenated olefins, depending upon their structures [cf., J. Phys. Chem., 44, 275(1940)]. Specifically, it reacts easily, e.g. with 1,1-dichloroethylene at 65.degree. C. [cf., J. Am. Chem. Soc., 65, 1271(1943)]. Further, hydrogen halide [HX; X=F, Cl, Br or I] is generally known as an electrophilic reagent. It is considered that in the addition reaction of olefin with hydrogen halide, ionized H.sup.+ initially attacks olefin and then X.sup.- reacts with carbonium cation formed as the intermediate. Hydrogen fluoride however reacts with a polyhalogenated olefin, with predominant nucleophilic attack of F.sup.-, thereby affording the desired product in good yield [J. Am. Chem. Soc., 82, 3091(1960)] . However, such nucleophilic reaction is not known for hydrogen chloride and hydrogen bromide. Accordingly, the reaction of 1,1-dihalogenoethylene with hydrogen chloride or hydrogen bromide whose reactivity is different from hydrogen fluoride is not suggested or predicted by the fact that 1,1-dihalogenoethylene as a kind of polyhalogenoolefin reacts easily with hydrogen fluoride.
Under these circumstances, the inventors of this invention have made various studies and have found unexpectedly the fact that when a 1,1-dihalogenoethylene is reacted with nitric acid or its salt and hydrogen chloride or hydrogen bromide or its salt, it provides at a high yield 1,1,1-trihalogeno-2-nitroethane (or 1-nitro-2,2,2-trihalogenoethane) in which a nitro group and a halogen atom are introduced at the same time and at the specific positions.
3. Summary of the Invention
This invention provides
1) a process for the production of 1,1,1-trihalogeno-2-nitroethanes which comprises reacting a 1,1-dihalogenoethylene of the formula (I): ##STR6## wherein X.sup.1 and X.sup.2 are the same or different and represent a fluorine, chlorine, bromine or iodine atom, with nitric acid or its salt and hydrogen chloride or hydrogen bromide or its salt to obtain a compound of the formula (II): ##STR7## wherein X.sup.1 and X.sup.2 have the same meanings as defined in the formula (I), and X.sup.3 is chlorine or bromine atom; PA1 2) a process for the production of .alpha.-unsaturated amines which comprises reacting a 1,1,1-trihalogeno-2-nitroethane of the formula (II) mentioned in the above 1) with an amino compound of the formula (III): EQU R.sup.1 --NH--C.sub.n H.sub.2n --A (III) PA1 3) a process for the production of .alpha.-unsaturated-amines which comprises treating a 1,1,1-trihalogeno-2-nitroethane of the formula (II) mentioned in the above 1) with a base to obtain a 1,1-dihalogeno-2-nitroethylene of the formula (VI): ##STR10## wherein X.sup.4 and X.sup.5 are the same or different and represent a fluorine, chlorine, bromine or iodine atom, and then reacting it with an amino compound of the formula (III): EQU R.sup.1 --NH--C.sub.n H.sub.2n --A (III) PA1 wherein R.sup.1, A and n have the same meanings as defined in the above 2), or its salt and an amino compound of the formula (IV): ##STR11## wherein R.sup.2 and R.sup.3 have the same meanings as defined in the above 2), or its salt to obtain a compound of the formula (V): ##STR12## wherein R.sup.1, R.sup.2, R.sup.3 A and n have the same meanings as mentioned above or its salt; PA1 3. Preferred Embodiments of the Invention
wherein R.sup.1 is a hydrogen atom, an C.sub.1-4 alkyl, halo-C.sub.1-4 alkyl, mono- or di-C.sub.1-4 alkoxy-C.sub.1-4 alkyl, C.sub.7-9 aralkyl, optionally substituted phenyl, mono- or di-C.sub.1-4 alkylamino or C.sub.1-4 alkoxy group, A is a 3- or 4-pyridyl, pyrazinyl, 2-, 4- or 5-thiazolyl or phenyl group which may be substituted by a halogen atom or a C.sub.1-4 alkyl, C.sub.1-4 alkylthio or C.sub.1-4 alkoxy group, and n is 0, 1 or 2, or its salt and an amino compound of the formula (IV): ##STR8## wherein R.sub.2 is a hydrogen atom, or a C.sub.1-4 alkyl or C.sub.7-9 aralkyl group, R.sub.3 is a hydrogen atom, a C.sub.1-5 alkyl, halo-C.sub.1-4 alkyl, hydroxy-C.sub.1-4 alkyl, mono- or di-C.sub.1-4 alkoxy-C.sub.1-4 alkyl, mono- or di-C.sub.1-4 alkylthio-C.sub.1-4 alkyl, di-C.sub.1-4 alkylamino-C.sub.1-4 alkyl, tri-C.sub.1-4 -alkylsilyl-C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.7-9 aralkyl, optionally substituted phenyl, amino, di-C.sub.1-4 alkylamino, pyridyl-C.sub.1-2 alkyl or thiazolyl-C.sub.1-2 alkyl group (pyridyl and thiazolyl ring may be substituted by a halogen atom), or R.sup.2 and R.sup.3 together with the adjacent nitrogen atom may form a 5 or 6-membered heterocylic ring which may contain an oxygen atom or another nitrogen atom, or its salt, to obtain a compound of the formula (V): ##STR9## wherein R.sup.1, R.sup.2, R.sup.3, A and n have the same meanings as defined above or its salt; and
With respect to R.sub.1 of the above mentioned formulas,
the C.sub.1-4 alkyl may be methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl or t-butyl, among which methyl, ethyl or n-propyl is preferable; PA0 the halo-C.sub.1-4 alkyl may be monochloromethyl, dichloromethyl, trichloromethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, 2-chloroethyl, 2,2,2-trichloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl or 1,1,2,2-tetrafluoroethyl; PA0 the mono- or di-C.sub.1-4 alkoxy-C.sub.1-4 alkyl group may be methoxymethyl, dimethoxymethyl, ethoxymethyl, 1- or 2-methoxyethyl, 2,2-dimethoxyethyl, 3-methoxypropyl or 3,3-dimethoxypropyl, among which methoxymethyl, dimethoxymethyl, 2-methoxyethyl or 2,2-dimethoxyethyl is preferable; PA0 the C.sub.7-9 aralkyl group may be benzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-methylbenzyl, phenethyl or 4-methylphenethyl; PA0 the optionally substituted phenyl group may be phenyl or a phenyl substituted by one to four substituents of a halogen (e.g., fluorine, chlorine, bromine or iodine), C.sub.1-3 alkyl (e.g., methyl, ethyl or propyl), C.sub.1-3 alkoxy (e.g., methoxy, ethoxy or propoxy), amino, hydroxy, carboxy or sulfo; PA0 the mono- di-C.sub.1-4 alkylamino group may be methylamino, ethylamino, n-propylamino, i-propylamino or n-butylamino, or dimethylamino, methylethylamino, diethylamino or di-n-propylamino; PA0 the C.sub.1-4 alkoxy group may be methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy or i-butoxy. PA0 the halo C.sub.1-4 alkyl, mono- or di-C.sub.1-4 alkoxyalkyl, C.sub.7-9 aralkyl, optionally substituted phenyl and di-C.sub.1-4 alkylamino groups include the same ones examplified in R.sup.1 ; PA0 the hydroxy C.sub.1-4 alkyl group may be hydroxymethyl, 1- or 2-hydroxyethyl, or 3-hydroxypropyl; PA0 the mono- or di-C.sub.1-4 alkylthio-C.sub.1-4 alkyl group may be methylthioethyl, ethylthioethyl, n-propylthioethyl methylthiopropyl, dimethylthiomethyl, diethylthiomethyl, dimethylthioethyl or dimethylthiopropyl; PA0 the di-C.sub.1-4 alkylamino-C.sub.1-4 alkyl group may be dimethylaminoethyl, diethylaminomethyl or dimethyl aminopropyl; PA0 the tri-C.sub.1-4 alkylsilyl-C.sub.1-4 alkyl group may be trimethylsilylmethyl, trimethylsilylethyl, trimethylsilylpropyl, triethylsilylmethyl or tri-n-propylsilylmethyl; PA0 the C.sub.2-4 alkenyl group may be vinyl, allyl or isopropenyl; PA0 the pyridyl-C.sub.1-2 alkyl group may be substituted by one to three halogens (e.g., Cl, Br or F) on the pyridine ring and includes e.g., (3-pyridyl)methyl, (6-chloro-3-pyridyl)methyl, (6-fluoro-3-pyridyl)methyl, (6-bromo-3-pyridyl)methyl and 1-(3-pyridyl)ethyl; PA0 the thiazolyl-C.sub.1-2 alkyl group may be substituted by one to three halogens (e.g., Cl, Br or F) on the thiazole ring and includes e.g., (2-thiazolyl)methyl, (5-thiazolyl)methyl, (2-chloro-5-thiazolyl)methyl, (2-bromo-5-thiazolyl)methyl, (4-thiazolyl)methyl and 1-(5-thiazolyl)ethyl. Preferable examples of R.sup.3 are hydrogen, or a C.sub.1-4 alkyl such as methyl, ethyl or propyl.
Preferable examples of R.sup.1 are hydrogen atom and a C.sub.1-4 alkyl group such as methyl, ethyl or propyl.
With respect to R.sup.2, the C.sub.1-4 alkyl group and C.sub.7-9 aralkyl group mentioned in R.sup.1 are applicable to these groups of R.sup.2. Preferable examples of R.sup.2 are hydrogen atom and a C.sub.1-4 alkyl group such as methyl, ethyl or propyl.
With respect to R.sup.3, the C.sub.1-5 alkyl group includes the C.sub.1-4 alkyl groups examplified in R.sup.1 and also amyl;
The 5- or 6-membered heterocyclic group which may contain an oxygen atom and another nitrogen atom (in addition to the adjacent nitrogen atom to R.sub.2 and R.sub.3) may be pyrrolidino, piperidino, morpholino, or 4-methylpiperazino.
With respect to A, the 3- or 4-pyridyl, pyrazinyl, 2-, 4- or 5-thiazolyl or phenyl group may be substituted by one to four substituents of a halogen, C.sub.1-4 alkyl, C.sub.1-4 alkylthio or C.sub.1-4 alkoxy. Here, the halogen may be fluorine, chlorine, bromine or iodine, the C.sub.1-4 alkyl or C.sub.1-4 alkoxy includes the same groups exemplified in R.sup.1 and the C.sub.1-4 alkylthio may be methylthio, ethylthio, n-propylthio, i-propylthio, n-butylthio or i-butylthio. Examples of the 3- or 4-pyridyl groups which may be substituted are 3-pyridyl, 2- or 6-chloro-3-pyridyl, 5- or 6-bromo-3-pyridyl, 6-fluoro-3-pyridyl, 6-methoxy-3-pyridyl, 6-methyl-3-pyridyl, 5- or 6-trifluoromethyl-3-pyridyl, 2-methylthio-3-pyridyl, 2,6- or 5,6-dichloro-3-pyridyl, 4-pyridyl and 2,6-dichloro-4-pyridyl. Examples of the 2,4- or 5-thiazolyl groups which may be substituted are 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-chloro-5-thiazolyl, 2-bromo-5-thiazolyl, 2-fluoro-5-thiazolyl, 2-methyl-5-thiazolyl, 2-trifluoromethyl-5-thiazolyl, 2,4-dichloro-5-thiazolyl and 2-phenyl-5-thiazolyl. Examples of the pyrazinyl groups which may be substituted are 2-pyrazinyl, 5-chloro-2-pyrazinyl 5-bromo-2-pyrazinyl, 5-fluoro-2-pyrazinyl 5-methoxy-2-pyrazinyl and 5-methyl-2-pyrazinyl Examples of the phenyl groups which may be substituted are phenyl, p-chlorophenyl, p-bromophenyl, p-fluorophenyl, p-tolyl and p-methoxyphenyl.
Preferable examples of A are 2-halogeno-5-thiazolyl such as 2-chloro-5-thiazolyl and 6-halogeno-3-pyridyl such as 6-chloro-3-pyridyl.
A preferable example of C.sub.n H.sub.2n is CH.sub.2.
Specific examples of the 1,1-dihalogenoethylenes (I) which are the starting material of this invention are 1,1-difluoroethylene, 1,1-dichloroethylene, 1,1-dibromoethylene, 1,1-diiodoethylene, 1-chloro-1-fluoroethylene, 1-bromo-1-fluoroethylene, 1-fluoro-1-iodoethylene, 1-bromo-1-chloroethylene, 1-chloro-1-iodoethylene and 1-bromo-1-iodoethylene, among which 1,1-dichloroethylene is useful because it is commercially available at a low price.
According to this invention, a 1,1-dihalogenoethylene (I) is reacted with nitric acid or its salt and hydrogen chloride or hydrogen bromide (hereinafter sometimes referred to as hydrogen halide) or its salt to obtain a 1,1,1-trihalogeno-2-nitroethane (II). Each of nitric acid and hydrogen halide is generally used in 0.5 to 5 equivalents, preferably 1.0 to 2.0 equivalents, more preferably 1.2 to 1.5 equivalents to the compound (I). In case of using a salt of hydrogen halide, further addition of nitric acid enough to generate the hydrogen halide is desirable to give a good result. Similarly, when a salt of nitric acid is used, further addition of hydrogen halide which is necessary for generating nitric acid will achieve a good result. Examples of the salts of the hydrogen halides or nitric acid are the alkaline metal salts, alkaline earth metal salts, and ammonium salt. Needless to say, it is possible to use the mixture of nitric acid and its salt or the hydrogen halide and its salt. The hydrogen halide can be used as it is but is conveniently used as its aqueous solution which is easy to handle, i.e., as hydrohalogenic acid. The concentration of each of nitric acid and the hydrogen halide to be used in the reaction is suitably selected, as far as it does not impede the reaction. As nitric acid, 60% to 70% nitric acid which is available on the market or a fuming nitric acid can be used. About 35% hydrochloric acid and about 47% hydrobromic acid which are available on the market can be used as hydrogen chloride and hydrogen bromide, respectively. These hydrohalogenic acids and nitric acid can be used by diluting with water, although it may cause the delay of the reaction speed. The preferred initial concentration of each of the hydrogen halide and nitric acid to be added in the reaction system is about 40% to 60%.
The reaction is usually carried out in an aqueous system, to which an inert organic solvent may be added. Examples of the organic solvents are those which are not easily mixable with water, such as hydrocarbons (e.g., hexane, petroleum ether, ligroin, cyclohexane, benzene, toluene, or xylene), ethers (e.g., diethyl ether or diisopropyl ether), esters (e.g., ethyl acetate) or halogenated hydrocarbons (e.g., chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane or 1,1-dihaloethylene as the starting material); those which are homogenerously mixable with water, such as nitriles (e.g., acetonitrile), tetrahydrofuran (hereinafter referred to as "THF") or dioxane.
The reaction can be conducted at 0.degree.-100.degree. C. in a sealed vessel but be conducted at 0.degree.-40.degree. C., preferably 10.degree.-35.degree. C. in an open system. The reaction time is 5 minutes or more, preferably 0.5 to 48 hours. However, the reaction time of 5 minutes or more, preferably 0.5 to 5 hours is sufficient in case where the preferred concentrations of the hydrogen halide and nitric acid and the preferred reaction temperature are selected.
The order of addition of the raw materials, i.e., the compound (I), nitric acid or its salt and the hydrogen halide or its salt in the reaction system can be optionally determined. That is, to the mixture of two optional kinds of the raw materials can be added the remaining raw material, or to one optional raw material can be added the remaining two raw materials at the same time. Alternatively, the three raw materials can be simultaneously mixed. We found the fact that nitric acid is reacted with the 1,1-dihalogenoethylene to produce the 1,1,1-trihalogeno- 2-nitroethane. For instance, when 1,1-dichloroethylene is reacted with 70% nitric acid, it affords the mixture of 1,1,1-trichloro-2-nitroethane and 1,1,1,2-tetrachloroethane as main products, which however is not satisfactory for yield. On the other hand, hydrochloric acid or hydrobromic acid is hardly reacted with the 1,1-dihalogenoethylene under the condition of the present invention. Thus, it will be understood that in accordance with the reaction of the present invention, the coexistence of nitric acid and the hydrogen halide is required to prepare the 1,1,1-trihalogeno-2-nitroethane (II) in high yield from the 1,1-dihalogenoethylene.
The completion of the reaction can be detected by the stop of an exothermic reaction, or the conventional analysis with an instrument such as gas chromatography, NMR, etc. The object compound (II) can be isolated by the conventional methods such as liquid separation, extraction and evaporation.
Examples of 1,1,1-trihalogeno-2-nitroethanes (II) thus obtained are 1,1,1-trichloro-2-nitroethane, 1-bromo-1,1-dichloro-2-nitroethane, 1,1-dibromo-1-chloro-2-nitroethane, 1-chloro-1,1-diiodo-2-nitroethane, 1,1-dichloro-1-fluoro-2-nitroethane, 1-chloro-1,1-difluoro-2-nitroethane, 1,1-dibromo-1-iodo-2-nitroethane, 1-bromo-1,1-diiodo-2-nitroethane, 1,1-dibromo-1-fluoro-2-nitroethane, 1-bromo-1,1-difluoro-2-nitroethane and 1,1,1-tribromo-2-nitroethane, among which especially 1,1,1-trichloro-2-nitroethane is industrially useful.
The 1,1,1-trihalogeno-2-nitroethane (II) is reacted with an amino compound of the formula (III): EQU R.sup.1 --NH--C.sub.n H.sub.2n --A (III)
wherein R.sup.1, A and n have the same meanings as defined above, or its salt and an amino compound of the formula (IV): ##STR13## wherein R.sup.2 and R.sup.3 have the same meanings as defined above, or its salt to provide an .alpha.-unsaturated amine of the formula (V): ##STR14## wherein R.sup.1, R.sup.2, R.sup.3, A and n have the same meanings as defined above or its salt.
The reaction is preferably conducted in the presence of a base, in order to avoid a consumption of the amino compound by a hydrogen halide which is produced as by-product of this reaction. Although there is no limitation of the order of addition of the two amino compounds (III) and (IV), it is preferable to conduct at first the reaction of a secondary amine in case of the combination of primary and secondary amines. Accordingly, it is possible to react the compound (II) with the compound (III), subsequently with the compound (IV), and alternatively to react the compound (II) with the compound (IV) followed by reacting with the compound (III).
Suitable examples of the bases to be employed in the reaction are organic bases such as triethylamine, tri-n-propylamine, pyridine, collidine, quinoline, dimethylaniline, methyldicyclohexylamine, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]-octane, 1,8-diazabicyclo[5.4.0]-7-undecene and 3,4-dihydro-2H-pyrido[1,2-a]-pyrimidin-2-one; inorganic bases such as sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide and calcium hydroxide; salts of carboxylic acids such as sodium acetate and potassium acetate. It is also possible to use as the base the amino compounds themselves which are used as the raw materials. The base is preferably used in 3 or more equivalents, to the compound (II), and there is no particular limitation in the timing of addition thereof as far as it does not impede the reacion.
The reaction is usually carried out in a solvent which does not impede the reaction. Suitable examples of the solvents are water; aliphatic hydrocarbons such as hexane, petroleum ether, ligroin and cyclohexane; aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene; alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol; halogenated hydrocarbons such as chloroform, dichloromethane, carbon tetrachloride and 1,2-dichloroethane, ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran; ketones such as acetone and methyl ethyl ketone; nitriles such as acetonitrile and propionitrile; amides such as dimethylformamide and dimethylacetamide; esters such as methyl acetate, ethyl acetate and butyl acetate, and sulfoxides such as dimethyl sulfoxide.
The reaction temperature can be selected from the range of -80.degree. C. or higher, but is generally -40.degree. C. or higher, preferably -40.degree. C. to 120.degree. C., more preferably -20.degree. C. to 50.degree. C. The reaction will be completed within a relatively short time of 5 minutes to 5 hours. The object compound (V) after completion of the reaction can be isolated by the conventional methods such as filtration, concentration, extraction and column chromatography.
Also, the .alpha.-unsaturated amine (V) or its salt can be obtained by treating a 1,1,1-trihalogeno-2-nitroethane (II) with a base to obtain a 1,1-dihalogeno-2-nitroethylene (VI) and then reacting the compound (VI) with or without isolation with the amino compounds (III) and (IV) or salts thereof. ##STR15##
The first reaction for obtaining the compound (VI) from the compound (II) and the base can be conducted with or without solvent. Suitable examples of the solvents to be employed are water; aliphatic hydrocarbons such as hexane, petroleum ether, ligroin and cyclohexane; aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene; alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol; halogenated hydrocarbons such as chloroform, dichloromethane, carbon tetrachloride and 1,2-dichloroethane; ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran; ketones such as acetone and methyl ethyl ketone; nitriles such as acetonitrile and propionitrile; amides such as dimethylformamide and dimethylacetamide; esters such as methyl acetate, ethyl acetate and butyl acetate; and sulfoxides such as dimethyl sulfoxide.
Examples of the bases to be employed in the reaction are organic bases such as triethylamine, tri-n-propylamine, pyridine, collidine, quinoline, dimethylaniline, methyldicyclohexylamine, 1,5-diazabicyclo[4.3.0]-non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 1,8-diazabicyclo[5.4.0]-7-undecene and 3,4-dihydro-2H-pyrido[1.2-a]pyrimidin-2-one; inorganic bases such as sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide and calcium hydroxide; salts of carboxylic acid salts such as sodium acetate and potassium acetate. Such bases are used in 1 to 5 equivalents, preferably 1 to 2 equivalents, to the compound (II). The reaction temperature can be selected in the range of -80.degree. C. or higher, but is generally -40.degree. C. or higher, preferably -40.degree. C. to 120.degree. C., more preferably -20.degree. C. to 50.degree. C.
The completion of the reaction can be detected, e.g. by gas chromatography, NMR, etc. The reaction will be completed within a relatively short time such as 15 minutes to 5 hours. For the isolation of the resulting product (VI), the conventional method such as extraction, filtration, concentration or evaporation is suitably utilized.
In the second reaction for obtaining the compound (V) from the compound (VI), the order of the reaction of two kinds of the amino compounds (III) and (IV) can be freely selected and, in case of the combination of a primary amine and a secondary amine, it is preferable to allow to firstly react the secondary amine. Any one of the compounds (III) and (IV) can be firstly used to react.
The reaction is preferably conducted in a solvent, to which those exemplified in the above mentioned first reaction are applicable. The reaction is preferably conducted in the presence of such base, to which those mentioned in the above mentioned first reaction are applicable. The base is used in 2 to 5 equivalents, preferably 2 to 3 equivalents, to the compound (VI). As occasion demands, it is also possible to use as such base the amino compound itself which is employed as the raw material. The reaction temperature can be chosen from the range of -80.degree. C. or higher, preferably -40.degree. C. to 120.degree. C. but is generally -40.degree. C. or higher, especially -20.degree. C. to 50.degree. C. The reaction time is relatively short and is 5 minutes to 5 hours.
The isolation of the resulting compound (V) after completion of the reaction can be carried out by the conventional method such as filtration, concentration, extraction and column chromatography.
In the above reactions, it is especially preferable to use secondary amines or salts thereof as either one or both of two kinds of the amino compounds (III) and (IV).
Examples of salts of the amino compounds (III) and (IV) are the salts with an inorganic acid such as hydrochloric acid, sulfuric acid or nitric acid; an organic acid such as benzenesulfonic acid; and a base such as sodium, potassium or lithium (e.g., C.sub.1-4 alkyl-N-(Na)C.sub.n H.sub.2n --A).
The amino compounds (III) and (IV) can be easily produced by the known methods, as described, e.g. in Organic Functional Group Preparations, Academic Press Vol 1, Chapter 13 (1968) and Vol 3, Chapter 10 (1972); survey of Organic Syntheses, Wiley-Inter-Science (1970), Chapter 8, or analogous methods thereto. Specific examples of the .alpha.-unsaturated-amines (V) as produced are shown in the Table 1.
TABLE 1 __________________________________________________________________________ ##STR16## Compound Melting No. R.sup.1 R.sup.2 R.sup.3 C.sub.n H.sub.2n A point __________________________________________________________________________ 1 H H Me CH.sub.2 ##STR17## 159-160 2 H H Et CH.sub.2 ##STR18## 161-162 3 H H i-Pr CH.sub.2 ##STR19## 148-150 4 H H n-Bu CH.sub.2 ##STR20## 110-112 5 H H Allyl CH.sub.2 ##STR21## 114-115 6 H H n-C.sub.5 H.sub.13 CH.sub.2 ##STR22## 97-98 7 H H ##STR23## CH.sub.2 ##STR24## 217-218 8 H H H CH.sub.2 ##STR25## 177-178 9 H H n-PrS(CH.sub.2).sub.2 CH.sub.2 ##STR26## 93-94 10 H H Me.sub.2 N(CH.sub.2).sub.2 CH.sub.2 ##STR27## 110-111 11 H H HO(CH.sub.2).sub.2 CH.sub.2 ##STR28## 161-163 12 H H MeO(CH.sub.2).sub.2 CH.sub.2 ##STR29## 108-109 13 H H (MeO).sub.2 CHCH.sub.2 CH.sub.2 ##STR30## 96-98 14 H H CF.sub.3 CH.sub.2 CH.sub.2 ##STR31## 164-165 15 H H Me.sub.3 SiCH.sub.2 CH.sub.2 ##STR32## 156-157 16 H H NH.sub.2 CH.sub.2 ##STR33## 176-177 decomposition 17 H Me Me CH.sub.2 ##STR34## 68-70 18 H (CH.sub.2).sub.4 CH.sub.2 ##STR35## 103-105 19 H ##STR36## CH.sub.2 ##STR37## oily form 20 H (CH.sub.2).sub.2O(CH.sub.2).sub.2 CH.sub.2 ##STR38## 102-103 21 H (CH.sub.2).sub.5 CH.sub.2 ##STR39## 106-108 22 H H Me.sub.2 N CH.sub.2 ##STR40## 158-159 23 Me H H CH.sub.2 ##STR41## 158-159 24 Me H Me CH.sub.2 ##STR42## 86-87 25 H H Me CH.sub.2 ##STR43## 181-183 26 Me H Me CH.sub.2 ##STR44## 103-104 27 Et H Me CH.sub.2 ##STR45## oily form 28 (MeO).sub.2 CHCH.sub.2 H Me CH.sub.2 ##STR46## oily form 29 Me H Et CH.sub.2 ##STR47## oily form 30 Me H n-Bu CH.sub.2 ##STR48## oily form 31 MeO(CH.sub.2).sub.2 H Me CH.sub.2 ##STR49## oily form 32 Me H Allyl CH.sub.2 ##STR50## oily form 33 Me H i-Pr CH.sub.2 ##STR51## 119-121 34 Me H ##STR52## CH.sub.2 ##STR53## oily form 35 Me H Me CH.sub.2 ##STR54## 145-147 36 Me H Me Me CH ##STR55## oily form 37 Me.sub.2 N H Me CH.sub.2 ##STR56## 109-110 38 n-Pr H Me CH.sub.2 ##STR57## oily form 39 n-Bu H Me CH.sub.2 ##STR58## oily form 40 ##STR59## H Me CH.sub.2 ##STR60## 118-119 41 Me H H CH.sub.2 ##STR61## 206-207 42 H Me Me CH.sub.2 ##STR62## 124-125 43 H H Me CH.sub.2 ##STR63## 211-213 decomposition 44 Me H H CH.sub.2 ##STR64## 214-215 decomposition 45 i-Pr H H CH.sub.2 ##STR65## powder 46 H Me Et CH.sub.2 ##STR66## 87-88 47 H H NH.sub.2 CH.sub.2 ##STR67## 188-190 decomposition 48 H H Me.sub.2 N CH.sub.2 ##STR68## 170-172 49 Me H Me CH.sub.2 CH.sub.2 ##STR69## oily form 50 Me Me Me CH.sub.2 ##STR70## 103-105 51 Me Me ##STR71## CH.sub.2 ##STR72## oily form 52 Me Me Me CH.sub.2 ##STR73## 110-112 53 Et H H CH.sub.2 ##STR74## 159-161 54 Et H Me CH.sub.2 ##STR75## 83-84 55 Me H Me CH.sub.2 ##STR76## 77-78 56 Me H Me CH.sub.2 ##STR77## 145-146 57 Me H Me CH.sub.2 ##STR78## 96-97 58 MeO H Me CH.sub.2 ##STR79## 100-101 59 Me H MeO(CH.sub.2).sub.2 CH.sub.2 ##STR80## 55-57 60 Me H Me CH.sub.2 ##STR81## 98-99 61 H H H CH.sub.2 ##STR82## 215-216 decomposition 62 H H Me CH.sub.2 ##STR83## 219-220 decomposition 63 H Me Me CH.sub.2 ##STR84## 133-135 64 Me H Me CH.sub.2 ##STR85## 132-133 65 Me H Me.sub.2 N CH.sub.2 ##STR86## 80-82 66 n-Pr H H CH.sub.2 ##STR87## 185-186 decomposition 67 n-Pr H Me CH.sub.2 ##STR88## 102-103 68 i-Pr H Me CH.sub.2 ##STR89## 119-120 69 Me H Me -- ##STR90## 108-109 70 Me H Me -- ##STR91## 113-114 71 Me H Et CH.sub.2 ##STR92## 132-133 72 Me H Me CH.sub.2 ##STR93## 131-133 73 Me H Me CH.sub.2 ##STR94## 106-113 74 Me H Me -- ##STR95## 155-156 75 Me H Me -- ##STR96## 120-121 76 Me H Et -- ##STR97## 118-119 77 Me H Me CH.sub.2 ##STR98## 116-117 78 Me H Me CH.sub.2 ##STR99## 131-132 79 Me H Me CH.sub.2 ##STR100## 155-156 80 H H ##STR101## CH.sub.2 ##STR102## 238-240 decomposition 81 Et H Me -- ##STR103## 95-95 82 n-Pr H Me -- ##STR104## 94-95 83 n-Bu H Me -- ##STR105## 87-88 84 Et H Et -- ##STR106## 105 85 Me H Me -- ##STR107## 114-115 86 Me H n-Pr -- ##STR108## oily form 87 H H Me -- ##STR109## 185 decomposition 88 Me H Me CH.sub.2 ##STR110## 102-103 89 Me H Me CH.sub.2 ##STR111## 100-100.5 90 Et H Me CH.sub.2 ##STR112## oily form 91 Me H Me CH.sub.2 ##STR113## 130-131 92 Et H Me CH.sub.2 ##STR114## 79-80 93 Me H Me CH.sub.2 ##STR115## 131-133 94 Et H Me CH.sub.2 ##STR116## 110-112 95 H Me Me CH.sub.2 ##STR117## 101-102 96 H H ##STR118## CH.sub.2 ##STR119## 211 decomposition 97 H H Me CH.sub.2 ##STR120## 181 decomposition 98 H Me Me -- ##STR121## 122-123 99 Me H Me -- ##STR122## 131-132 100 H H Me CH.sub.2 ##STR123## 184-186 decomposition 101 H Me Me CH.sub.2 ##STR124## 158-159 102 Me H H CH.sub.2 ##STR125## 206-207 103 CF.sub.3 CH.sub. 2 H Me CH.sub.2 ##STR126## 110-111 104 H H Me CH.sub.2 ##STR127## 182-184 decomposition 105 H H Me CH.sub.2 ##STR128## 167-169 decomposition 106 H Me Me CH.sub.2 ##STR129## 125 decomposition 107 Et Me Me CH.sub.2 ##STR130## oily form 108 CH.sub.2 FCH.sub.2 H Me CH.sub.2 ##STR131## 78-79 109 CH.sub.2 FCH.sub.2 Me Me CH.sub.2 ##STR132## 90-91 110 CH.sub. 2 FCH.sub.2 H Me CH.sub.2 ##STR133## 111 CH.sub.2 FCH.sub.2 Me Me CH.sub.2 ##STR134## 112 CH.sub.2 FCH.sub.2 H Me CH.sub.2 ##STR135## 113 Me Me Me CH.sub.2 ##STR136## 114 Et Me Me CH.sub.2 ##STR137## 115 Me H Me CH.sub.2 ##STR138## 116 Et H Me CH.sub.2 ##STR139## 117 CH.sub.2 FCH.sub.2 Me Me CH.sub.2 ##STR140## 118 Me Me Me CH.sub.2 ##STR141## 119 Et Me Me CH.sub.2 ##STR142## 120 ClCH.sub.2 H Me CH.sub.2 ##STR143## 121 ClCH.sub.2 H Me CH.sub.2 ##STR144## 122 ClCH.sub.2 H Me CH.sub.2 ##STR145## 123 CH.sub.2 FCH.sub.2 H Me CH.sub.2 ##STR146## 124 CH.sub.2 FCH.sub.2 Me Me CH.sub.2 ##STR147## 125 CF.sub.3 CH.sub.2 H Me CH.sub.2 ##STR148## 126 CF.sub.3 CH.sub.2 Me Me CH.sub.2 ##STR149## 127 Me Me Me CH.sub.2 ##STR150## 128 Et Me Me CH.sub.2 ##STR151## 129 H H Me CH.sub.2 ##STR152## 130 H Me Me CH.sub.2 ##STR153## 131 Me Me Me CH.sub.2 ##STR154## 132 Et Me Me CH.sub.2 ##STR155## 133 Et (CH.sub.2).sub.4 CH.sub.2 ##STR156## 110-111 134 Et Et Et CH.sub.2 ##STR157## 105-106 135 Et H i-Pr CH.sub.2 ##STR158## 126-127.5 136 Et H t-Bu CH.sub.2 ##STR159## 151-152 137 CH.sub.2 FCH.sub.2 H H CH.sub.2 ##STR160## 152-153 138 Et H Et CH.sub.2 ##STR161## 123-125 139 Et H ##STR162## CH.sub.2 ##STR163## 74-75 140 Et MeO Me CH.sub.2 ##STR164## oily form 141 Et MeO H CH.sub.2 ##STR165## oily form 142 Et Me Et CH.sub.2 ##STR166## oily form 143 Et H Me.sub.2 N CH.sub.2 ##STR167## oily form 144 ##STR168## H Me CH.sub.2 ##STR169## 115-116 145 ##STR170## H H CH.sub.2 ##STR171## oily form 146 ##STR172## H H CH.sub.2 ##STR173## 128-129 147 ##STR174## Me Me CH.sub.2 ##STR175## oily form 148 ##STR176## Me Me CH.sub.2 ##STR177## 73-75 149 Et H Me CH.sub. 2 ##STR178## 108-109 __________________________________________________________________________ ##STR179## ##STR180##
In the above table, Me, Et, n-Pr, i-Pr and n-Bu represent CH.sub.3 --, CH.sub.3 CH.sub.2 --, CH.sub.3 CH.sub.2 CH.sub.2 --, ##STR181##
When the compound (V) is obtained in the free form, it may be converted into its salt form by the conventional method and, on the contrary, the salt when obtained may be converted into the corresponding free form by the conventional method. That is, when the compound (V) has a basic group or moiety in the parts of R.sup.1, R.sup.3 and A, it may form the acid addition salt, e.g., the hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, phosphate, acetate, benzoate, maleate, fumalate, succinate, tartarate, citrate, oxalate, glyoxylate, aspartate, methanesulfonate, methanedisulfonate, 1,2-ethanedisulfonate or benzenesulfonate. Also, the compound (V) may form an inner salt which is also included in this invention.
The compounds (V) can exist as stereoisomers and tautomers, and such isomers and mixtures thereof are also included in this invention.
The compounds (V) or their salts are effective in preventing sanitary or horticultural insect pests and animal and plant parasites and can exert potent insecticidal activities when they are directly contacted with insects, e.g., by applying to their living animals or plants. An interesting characteristic property of the compounds (V) or their salts is found in that potent insecticidal activities can be achieved by once absorbing the compounds in plants through their root, leaves or stem which are then sucked or bitten by insects or contacted with insects. Such property is Advantageous for preventing suctorial type or mandible type insecticides. Moreover, the compounds (V) and their salts possess safe and advantageous properties as agents for preventing agricultural injurious insects, such as no substantial damage on plants and less toxicity against fishes.
Specifically, the preparations containing the compounds (V) or their salts are especially effective in preventing Hemiptera injurious insects such as Eurydema rugosum, Scotinophara lurida, Riptortus clavatus, Stephanitis nashi, Laodelphax striatellus, Nalaparvate lugens, Nephotettix cincticeps, Unaspis yanonensis, Aphis glycines, Lipaphis erysimi, Brevicoryne brassicae, Aphis gissypii, Sogattela furcifera, Nezara viridula, Trialeurodes vaporariorum, Myzus persicae, Pseudococcus comstocki, Aphis promi Nezara spp, Cimex lectularius and Psylla spp; Lepidoptera injurious insects such as Spodoptera litura, Plutella xylostella, Pieris rapae crucivora, Chilo suppressalis, Autographa nigrisigna, Helicoverpa assulta, Pseudaletia separata, Mamestra brassicae, Adoxophyes orana fasciata, Notarcha derogata, Cnaphalocrocis medinalis and Phthorimaea operculella; Coleoptera injurious insects such as Epilachna vigintioctopunctata, Aulacophora, femoralis, Phyllotreta striotata, Oulema oryzae and Echinocnemus squameus; Diptera injurious insects such as Musca domestica, Culex pipiens pallens, Tabanus trigonus, Delia antiqua and Delia platura; Orthoptera injurious insects such as Locusta migratoria and Gryllotalpa africana; Dictyoptera injurious insects such as Blattella germanica and Periplaneta fuliginosa; Tetranychidaes such as Tetranychus urticae, Panonychus citri, Tetranychus kanzawai, Tetranychus cinnabarinus, Panonychus ulmi and Aculops pelekassi; and Nematodes such as Aphelenchoides besseyi.
The compounds (V) or their salts can be used as insecticides or miticides in any application form suited for general agricultural chemicals. That is, one, two, or more than two kinds of the compounds (V) or their salts are used in the form of preparation such as emulsifiable concentrates, oil solutions, wettable powders, dusts, granules, tablets, sprays or ointments, according to the purpose of use, by dissolving or dispersing them in suitable liquid carriers, or mixing them with or absorbing them on suitable solid carriers. These preparations may contain, if necessary, emulsifying agent, suspending agent, spreading agent, penetrating agent, wetting agent, thickening agent or stabilizer, and can be prepared by any conventional method known per se.
The rate of the compound (V) or a salt thereof contained in an insecticidal preparation is suitably about 10 to 90% by weight in the case of emulsifiable concentrates or wettable powders, about 0.1 to 10% by weight in the case of oil solution or dust and about 1 to 20% by weight in the case of granules. However, such concentration may be changed properly, depending on the purpose of use. Emulsifiable concentrates, wettable powders or the like are suitably diluted or extended (for example, to 10 to 100000 times) with water or the like, on the occasion or use, and then scattered.
Suitable examples of the liquid carriers (solvents) include solvents such as water, alcohols (for example, methanol, ethanol, n-propanol, isopropanol or ethylene glycol), ketones (for example, acetone or methyl ethyl ketone), ethers (for example, dioxane, tetrahydrofuran, ethylene glycol monomethyl ether, di-ethylene glycol monomethyl ether or propylene glycol monomethyl ether), aliphatic hydrocarbons (for example, kerosine, kerosene oil, fuel oil or machine oil), aromatic hydrocarbons (for example, benzene, toluene, xylene, solvent naphtha or methylnaphthalene), halogenated hydrocarbons (for example, dichloromethane, chloroform or carbon tetrachloride), acid amides (for example, dimethylformamid or dimethyl acetamide), esters (for example, ethyl acetate, butyl acetate or fatty acid glycerol ester )or nitriles (for example, acetonitrile or propionitrile). These solvents are used individually or as a suitable mixture of two, or more, of them.
Suitable examples of the solid carriers (diluents or dust carrier) include vegetable powder (for example, soybean meal, tobacco meal, wheat flour or wood flour), mineral powders (for example, clays such as kaolin, bentonite, or acid clay, talcs such as talc powder or pyrophyllite powder), silicas (for example, diatomaceous earth or mica powder), aluminas, sulfur powder or active carbon. They are used individually or as a suitable mixture of two, or more, of them.
Also, suitable examples of bases for ointments include polyethylene glycol, pectin, polyalcohol esters of higher aliphatic acids (for example, glycerin mono-stearate), cellulose derivatives (for example, methyl cellulose), sodium alginate, bentonite, higher alcohols, polyalcohos (for example, glycerin), vaseline, white petrolatum, liquid paraffin, lard, various vegetable oils, lanolin, dehydrated lanolin, hard oil or resins. They are used individually, or as a suitable mixture of two, or more, of them or together with surface active agents mentioned below.
As surface active agents used as the emulsifying agent, spreading agent, penetrating agent or dispersing agent, nonionic or anionic surface active agents such as soaps; polyoxyethylene alkyl aryl ethers (e.g., Noigen.RTM. and E.A 142.RTM. from Dai-ichi Kogyo Seiyaku K.K., Japan, and Nonal.RTM. from Toho Chemical, Japan); alkyl sulfates (e.g., Emal 10.RTM. and Emal 40.RTM. from Kao K.K., Japan); alkyl sulfonates (e.g., Neogen.RTM. and Neogen T.RTM. from Dai-ichi Kogyo Seiyaku K.K. and Neopellex.RTM. from Kao K.K.); polyethylene glycol ethers (e.g., Nonipol 85.RTM., Nonipol 100.RTM., Nonipol 160.RTM. from Sanyo Kasei K.K., Japan); or polyhydric alcohol esters (e.g., Tween 20.RTM. and Tween 80.RTM. from Kao K.K.) are used, if necessary.
The compounds (V) or their salts can also be used, as occasion demands, in combination with or as an admixture with other insecticides (for example, pyrethroid insecticides, organophosphorus insecticides, carbamate insecticides or natural insecticides), acaricides, nematocides, herbicides, plant hormones, plant growth regulators, fungicides (for example, copper fungicides, organic chlorine fungicides, organic sulfur fungicides or phenol fungicides), synergistic agents, attractants, repellents, pigments and/or fertilizers.
The insecticidal or miticidal composition comprising the compound (V) or its salt of the present invention is an excellent agricultural product having fairly low toxicity and good safety. It can be used in a similar way to the conventional insecticidal or miticidal composition and can exert excellent effects in comparison with the conventional compositions. For example, the insecticidal or miticidal compositions of the present invention can be applied to the target insects, by treatment in nursery box, application for stem and leaf of crop, spraying for insects, application in water of a paddy field or soil treatment of a paddy field. The amount of application may broadly vary depending on the season, place and method of application, and so forth. However, the active ingredient (the compound (V) or its salt) is used in general, in an amount of 0.3 g to 3,000 g, preferably 50 g to 1,000 g per hectare. When the insecticidal composition of the present invention is in a wettable powder, it can be used by diluting it so as to be 0.1- 1000 ppm, preferably 10-500 ppm as the final concentration of the active ingredient.
Activity
As will be clear from the following tests, the compounds (I) and salts thereof possess excellent insecticidal activities.